Aspalathin: a rare dietary dihydrochalcone from Aspalathus linearis (rooibos tea)

Abstract

Aspalathin (2′,3,4,4′,6′-pentahydroxy-3′-C-β-D-glucopyranosyldihydrochalcone) is a natural C-linked glucosyl dihydrochalcone present in Aspalathus linearis (Burm.f.) R.Dahlgren (rooibos), a South African endemic plant, popularly consumed globally as a herbal tea. Aspalathin is reported to possess potent anti-oxidant properties that are believed to be responsible for the health benefits of rooibos. Other pharmacological properties ascribed to the molecule include antidiabetic, antimutagenic, anti-inflammatory, antithrombotic, and xanthine oxidase inhibitory activities. The role of aspalathin in limiting the progression of metabolic disorders and preventing diabetes-induced cardiovascular complications has been reported. The aforementioned potential health benefits of aspalathin have rendered it a popular natural ingredient that is incorporated in various nutraceutical and cosmeceutical products for protection against different conditions. Percutaneous permeation studies revealed some degree of absorption through the skin, supporting its use in cosmetic preparations. To perform an in-depth assessment of the scientific literature available on aspalathin, a bibliometric analysis was carried out on publications for the period 1965–2020, using the Scopus database. A total of 140 articles were retrieved, indicating that South African authors are major contributors to aspalathin research. The most common areas of investigation were identified as anti-oxidation, chemistry/chemical profiling, antidiabetic and anti-inflammatory activities. A comprehensive literature search showed that there are currently only two available reviews on aspalathin. Hence, the present review aims to explore the history and fill gaps with regards to collating aspects of the synthesis, quality control, metabolism and various biological activities of the molecule.

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Abbreviations

A4:

Androstenedione

2-AAF:

2-Acetylaminofluorene

ABTS:

2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)

ACC:

Acetyl-CoA carboxylase

ADP:

Adenosine diphosphate

AFB1:

Aflatoxin B1

AGE:

Advanced glycation end product

AMPK:

Phosphorylation of AMP-activated protein kinase

ATP:

Adenosine triphosphate

AO:

Aortic output

ARRE:

Aspalathin-rich rooibos extract

Asp:

Aspalathin

ATV:

Atorvastatin

AUC:

Area under the curve

BHA:

Butylated hydroxyanisole

BHT:

Butylated hydroxytoluene

BW:

Body weight

CAMs:

Cell adhesion molecules

CLP:

Cecal ligation puncture

CPT1:

Carnitine palmitoyltransferase1

DAD:

Diode array detection

DCF:

2′,7′-Dichlorofluorescein diacetate

ddY:

Deutschland, Denken, and Yoken

DFT:

Density functional theory

DMAP:

4-(Dimethylamino)pyridine

DMF:

Dimethylformamide

DNA:

Deoxyribonucleic acid

Dox:

Doxorubicin

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

DSS:

Dextran sodium sulfate

EPCR:

Endothelial cell protein C receptor

FAO:

Fatty acid β-oxidation

FFA:

Free fatty acid

FL:

Fluorescein

FPG:

Fasting plasma glucose

FRAP:

Ferric reducing antioxidant power

FRE:

Fermented rooibos extract

FT:

Fourier Transform

G6Pase:

Glucose-6-phosphatase

GAE:

Gallic acid equivalents

GLUT:

Glucose transporter

GP:

Glycogen phosphorylase

GRE:

Green rooibos extract

GRT:

Aspalathin-rich rooibos extract

GS:

Glycogen synthase

GSG:

Glutathione

GSSG:

Oxidised glutathione

HG:

High glucose

hSGLT2:

Human sodium glucose co-transporter 2

HPLC:

High-performance liquid chromatography

HUVECs:

Human umbilical vein endothelial cells

HW/BW:

Heart weight to body weight

11βOH-A4:

11-Hydroxyandrostenedione

IC50 :

Half maximal inhibitory concentration

IPGTT:

Intraperitoneal glucose tolerance test

IRI:

Ischemia–reperfusion injury

JC-1:

5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylimidacarbocyanine iodide

LC–MS/MS:

Liquid chromatography-tandem mass spectrometry

LPO:

Lipid hydroperoxide

LPS:

Lipopolysaccharide

LDL:

Low-density lipoprotein

MBN:

Methylbenzylnitrosamine

MDCK:

Madin-Darby canine kidney

MRM:

Multiple reaction monitoring

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NADPH:

Nicotinamide adenine dinucleotide phosphate

NG:

Normal glucose

NIR:

Near infrared

NMR:

Nuclear magnetic resonance

Not:

Nothofagin

ORAC:

Oxygen radical absorbance capacity

pAMPK (Thr172):

Adenosine monophosphate-activated protein kinase threonine-172

PI3K:

Phosphatidylinositol 3-kinase

Papp:

Apparent rate of permeability

PARP:

Poly (adenosine diphosphate ribose) polymerase

PC:

Protein C

PCR:

Polymerase chain reaction

PEPK:

Phosphoenolpyruvate carboxykinase

PgP:

P-glycoprotein

PGR:

Pyrogallol red

PPAG:

Phenylpyruvic acid-2-O-β-D-glucoside

Rf:

Fermented rooibos aqueous extract

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

SCD:

Stearoyl-coenzyme A desaturase

scrRNA:

Scrambled ribonucleic acid

SGLT:

Sodium glucose co-transporter

siNrf2:

Small interfering nuclear factor erythroid 2-related factor 2

SOD:

Superoxide dismutase

STRING:

Search Tool for the Retrieval of Interacting Genes/Proteins

STZ:

Streptozotocin

TAC:

Total antioxidant capacity

TE:

Trolox equivalent

THF:

Tetrahydrofuran

TLC:

Thin-layer chromatography

UPLC-PDA:

Ultra performance liquid chromatography coupled to photodiode array detector

TMSOTf:

Trimethylsilyl trifluoromethanesulfonate

TPA:

12-O-Tetradecanoylphorbol-13-acetate

UCP2:

Uncoupling protein 2

XOD:

Xanthine oxidase inhibition

References

  1. Abrahams S, Samodien S, Lilly M et al (2019) Differential modulation of gene expression encoding hepatic and renal xenobiotic metabolizing enzymes by an aspalathin-enriched rooibos extract and aspalathin. Planta Med 85:6–13

    CAS  Article  Google Scholar 

  2. Ayeleso A, Brooks N, Oguntibeju O (2014) Modulation of antioxidant status in streptozotocin-induced diabetic male wistar rats following intake of red palm oil and/or rooibos. Asian Pac J Trop Med 7:536–544. https://doi.org/10.1016/S1995-7645(14)60090-0

    CAS  Article  PubMed  Google Scholar 

  3. Baba H, Ohtsuka Y, Haruna H et al (2009) Studies of anti-inflammatory effects of Rooibos tea in rats. Pediatr Int 51:700–704. https://doi.org/10.1111/j.1442-200X.2009.02835.x

    Article  PubMed  Google Scholar 

  4. Bae JS (2016) Aspalathin and nothofagin for preventing or treating sepsis. Republic of Korea KR 1615891(B1):20160427

    Google Scholar 

  5. Baranska M, Schulz H, Joubert E, Manley M (2006) In situ flavonoid analysis by FT-Raman spectroscopy: Identification, distribution, and quantification of aspalathin in green rooibos (Aspalathus linearis). Anal Chem 78:7716–7721. https://doi.org/10.1021/ac061123q

    CAS  Article  PubMed  Google Scholar 

  6. Beelders T, Sigge GO, Joubert E et al (2012) Kinetic optimisation of the reversed phase liquid chromatographic separation of rooibos tea (Aspalathus linearis) phenolics on conventional high performance liquid chromatographic instrumentation. J Chromatogr A 1219:128–139. https://doi.org/10.1016/j.chroma.2011.11.012

    CAS  Article  PubMed  Google Scholar 

  7. Bowles S, Joubert E, de Beer D et al (2017) Intestinal transport characteristics & metabolism of C-glucosyl dihydrochalcone, aspalathin. Molecules 22:1–15. https://doi.org/10.3390/molecules22040554

    CAS  Article  Google Scholar 

  8. Bramati L, Aquilano F, Pietta P (2003) Unfermented Rooibos tea: quantitative characterization of flavonoids by HPLC-UV and determination of the total antioxidant activity. J Agric Food Chem 51:7472–7474. https://doi.org/10.1021/jf0347721

    CAS  Article  PubMed  Google Scholar 

  9. Bramati L, Minoggio M, Gardana C et al (2002) Quantitative characterization of flavonoid compounds in Rooibos tea (Aspalathus linearis) by LC-UV/DAD. J Agric Food Chem 50:5513–5519. https://doi.org/10.1021/jf025697h

    CAS  Article  PubMed  Google Scholar 

  10. Breiter T, Laue C, Kressel G et al (2011) Bioavailability and antioxidant potential of rooibos flavonoids in humans following the consumption of different rooibos formulations. Food Chem 128:338–347. https://doi.org/10.1016/j.foodchem.2011.03.029

    CAS  Article  PubMed  Google Scholar 

  11. Chen W, Sudji IR, Wang E et al (2013) Ameliorative effect of aspalathin from rooibos (Aspalathus linearis) on acute oxidative stress in Caenorhabditis elegans. Phytomedicine 20:380–386. https://doi.org/10.1016/j.phymed.2012.10.006

    CAS  Article  PubMed  Google Scholar 

  12. Chrousos GP (2009) reviews Stress and disorders of the stress system. Nat Publ Gr 5:374–381. https://doi.org/10.1038/nrendo.2009.106

    CAS  Article  Google Scholar 

  13. Courts FL, Williamson G (2009) The C-glycosyl flavonoid, aspalathin, is absorbed, methylated and glucuronidated intact in humans. Mol Nutr Food Res 53:1104–1111. https://doi.org/10.1002/mnfr.200800569

    CAS  Article  PubMed  Google Scholar 

  14. Dawson J, Quinn T, Walters M (2007) Uric acid reduction: a new paradigm in the management of Cardiovascular risk? Curr Med Chem 14:1879. https://doi.org/10.2174/092986707781058797

    CAS  Article  PubMed  Google Scholar 

  15. de Beer D, Miller N, Joubert E (2017) Production of dihydrochalcone-rich green rooibos (Aspalathus linearis) extract taking into account seasonal and batch-to-batch variation in phenolic composition of plant material. South African J Bot 110:138–143. https://doi.org/10.1016/j.sajb.2016.02.198

    CAS  Article  Google Scholar 

  16. De Beer D, Tobin J, Walczak B et al (2019) Phenolic composition of rooibos changes during simulated fermentation: effect of endogenous enzymes and fermentation temperature on reaction kinetics. Food Res Int 121:185–196. https://doi.org/10.1016/j.foodres.2019.03.041

    CAS  Article  PubMed  Google Scholar 

  17. Dludla PV, Gabuza KB, Muller CJF et al (2018) Aspalathin, a C-glucosyl dihydrochalcone from rooibos improves the hypoglycemic potential of metformin in type 2 diabetic (db/db) mice. Physiol Res 67:813–818. https://doi.org/10.33549/physiolres.933891

    CAS  Article  PubMed  Google Scholar 

  18. Dludla PV, Muller CJF, Joubert E et al (2017) Aspalathin protects the heart against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression. Molecules 22:129. https://doi.org/10.3390/molecules22010129

    CAS  Article  PubMed Central  Google Scholar 

  19. Dludla P V., Muller CJF, Louw J, et al (2020) The combination effect of aspalathin and phenylpyruvic acid-2-o-β-d-glucoside from rooibos against hyperglycemia-induced cardiac damage: An in vitro study, Nutrients, 12https://doi.org/10.3390/nu12041151

  20. Erlwanger KH, Ibrahim KG (2017) Aspalathin a unique phytochemical from the South African rooibos plant (Aspalathus linearis): a mini review. J Afr Ass Physiol Sci 5:1–6

    Google Scholar 

  21. Fantoukh OI, Dale OR, Parveen A et al (2019) Safety assessment of phytochemicals derived from the globalized south african rooibos tea (Aspalathus linearis) through interaction with CYP, PXR, and P-gp. J Agric Food Chem 67:4967–4975. https://doi.org/10.22201/fq.18708404e.2004.3.66178

    CAS  Article  PubMed  Google Scholar 

  22. Fisher D, Thomas KA, Abdul-Rasool S (2020) The synergistic and neuroprotective effects of alcohol–antioxidant treatment on blood–brain barrier endothelial cells. Alcohol Clin Exp Res 44:1997–2007. https://doi.org/10.1111/acer.14433

    CAS  Article  PubMed  Google Scholar 

  23. von Gadow A, Joubert E, Hansmann CF (1997) Comparison of the antioxidant activity of aspalathin with that of other plant phenols of rooibos tea (Aspalathus linearis), α-Tocopherol, BHT, and BHA. J Agric Food Chem 45:632–638. https://doi.org/10.1021/jf960281n

    Article  Google Scholar 

  24. Han Z, Achilonu MC, Kendrekar PS et al (2014) Concise and scalable synthesis of aspalathin, a powerful plasma sugar-lowering natural product. J Nat Prod 77:583–588. https://doi.org/10.1021/np4008443

    CAS  Article  PubMed  Google Scholar 

  25. Hawkins HJ, Malgas R, Biénabe E (2011) Ecotypes of wild rooibos (Aspalathus linearis (Burm. F) Dahlg., Fabaceae) are ecologically distinct. South African J Bot 77:360–370. https://doi.org/10.1016/j.sajb.2010.09.014

    Article  Google Scholar 

  26. Huang M, Du Plessis J, Du Preez J et al (2008) Transport of aspalathin, a rooibos tea flavonoid, across the skin and intestinal epithelium. Phyther Res 22:699–704. https://doi.org/10.1002/ptr.2422

    CAS  Article  Google Scholar 

  27. Huang SH, Kao YH, Muller CJF et al (2020) Aspalathin-rich green Aspalathus linearis extract suppresses migration and invasion of human castration-resistant prostate cancer cells via inhibition of YAP signaling. Phytomedicine 69:153210. https://doi.org/10.1016/j.phymed.2020.153210

    CAS  Article  PubMed  Google Scholar 

  28. Huang SH, Tseng JC, Lin CY et al (2019) Rooibos suppresses proliferation of castration-resistant prostate cancer cells via inhibition of Akt signaling. Phytomedicine 64:153068. https://doi.org/10.1016/j.phymed.2019.153068

    CAS  Article  PubMed  Google Scholar 

  29. Human C, de Beer D, Aucamp M et al (2020) Preparation of rooibos extract-chitosan microparticles: Physicochemical characterisation and stability of aspalathin during accelerated storage. Lwt 117:108653. https://doi.org/10.1016/j.lwt.2019.108653

    CAS  Article  Google Scholar 

  30. Johnson R, De BD, Dludla PV et al (2018) Aspalathin from rooibos (Aspalathus linearis): a bioactive c -glucosyl dihydrochalcone with potential to target the metabolic syndrome. Planta Med 84:568–583. https://doi.org/10.1055/s-0044-100622

    CAS  Article  PubMed  Google Scholar 

  31. Johnson R, Dludla P, Joubert E et al (2016) Aspalathin, a dihydrochalcone C-glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis. Mol Nutr Food Res 60:922–934. https://doi.org/10.1002/mnfr.201500656

    CAS  Article  PubMed  Google Scholar 

  32. Johnson R, Dludla PV, Muller CJF et al (2017a) The transcription profile unveils the cardioprotective effect of aspalathin against lipid toxicity in an in vitro h9c2 model. Molecules 22:219. https://doi.org/10.3390/molecules22020219

    CAS  Article  PubMed Central  Google Scholar 

  33. Johnson R, Shabalala S, Louw J, et al (2017b) Aspalathin reverts doxorubicin-induced cardiotoxicity through increased autophagy and decreased expression of p53/mTOR/p62 signaling, Molecules. 22https://doi.org/10.3390/molecules22101589

  34. Joubert E (1996) HPLC quantification of the dihydrochalcones, aspalathin and nothofagin in rooibos tea (Aspalathus linearis) as affected by processing. Food Chem 55:403–411. https://doi.org/10.1016/0308-8146(95)00166-2

    CAS  Article  Google Scholar 

  35. Joubert E, de Beer D (2011) Rooibos (Aspalathus linearis) beyond the farm gate: from herbal tea to potential phytopharmaceutical. South African J Bot 77:869–886. https://doi.org/10.1016/j.sajb.2011.07.004

    Article  Google Scholar 

  36. Joubert E, Gelderblom WCA, Louw A, de Beer D (2008) South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides-a review. J Ethnopharmacol 119:376–412. https://doi.org/10.1016/j.jep.2008.06.014

    CAS  Article  PubMed  Google Scholar 

  37. Joubert E, Schulz H (2006) Production and quality aspects of rooibos tea and related products. a review. J Appl Bot Food Qual 80:138–144

    CAS  Google Scholar 

  38. Joubert E, Winterton P, Britz TJ, Ferreira D (2004) Superoxide anion and α, α-diphenyl-β-picrylhydrazyl radical scavenging capacity of rooibos (Aspalathus linearis) aqueous extracts, crude phenolic fractions, tannin and flavonoids. Food Res Int 37:133–138

    CAS  Article  Google Scholar 

  39. Joubert E, Winterton P, Britz TJ, Gelderblom WCA (2005) Antioxidant and pro-oxidant activities of aqueous extracts and crude polyphenolic fractions of rooibos (Aspalathus linearis). J Agric Food Chem 53:10260–10267. https://doi.org/10.1021/jf051355a

    CAS  Article  PubMed  Google Scholar 

  40. Joubert E, Gelderblom WCA, De Beer D (2009) Phenolic contribution of South African herbal teas to a healthy diet. Nat Prod Commun 4:701–718

    CAS  PubMed  Google Scholar 

  41. Kamakura R, Son MJ, de Beer D et al (2015) Antidiabetic effect of green rooibos (Aspalathus linearis) extract in cultured cells and type 2 diabetic model KK-A(y) mice. Cytotechnology 67:699–710. https://doi.org/10.1007/s10616-014-9816-y

    CAS  Article  PubMed  Google Scholar 

  42. Kawano A, Nakamura H, Hata SI et al (2009) Hypoglycemic effect of aspalathin, a rooibos tea component from Aspalathus linearis, in type 2 diabetic model db/db mice. Phytomedicine 16:437–443

    CAS  Article  Google Scholar 

  43. Kazuno S, Yanagida M, Shindo N, Murayama K (2005) Mass spectrometric identification and quantification of glycosyl flavonoids, including dihydrochalcones with neutral loss scan mode. Anal Biochem 347:182–192. https://doi.org/10.1016/j.ab.2005.09.020

    CAS  Article  PubMed  Google Scholar 

  44. Kinne RKH, Castaneda F (2011) SGLT inhibitors as new therapeutic tools in the treatment of diabetes. Handb Exp Pharmacol 203:105–126. https://doi.org/10.1007/978-3-642-17214-4_5

    CAS  Article  Google Scholar 

  45. Koeppen BH, Roux DG (1966) C-glycosylflavonoids. The Chem Aspalathin Biochem J 99:604–609. https://doi.org/10.1042/bj0990604

    CAS  Article  Google Scholar 

  46. Koeppen BH, Smit JB, Roux DG (1962) The flavone C-glycosides and flavonol O-glycosides of Aspalathus acuminatus (rooibos tea). Biochem J 83:507–511. https://doi.org/10.1042/bj0830507

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. Kondo M, Hirano Y, Nishio M et al (2013) Xanthine oxidase inhibitory activity and hypouricemic effect of aspalathin from unfermented rooibos. J Food Sci 78:H1935–H1939. https://doi.org/10.1111/1750-3841.12304

    CAS  Article  PubMed  Google Scholar 

  48. Krafczyk N, Glomb MA (2008) Characterization of phenolic compounds in rooibos tea. J Agric Food Chem 56:3368–3376. https://doi.org/10.1021/jf703701n

    CAS  Article  PubMed  Google Scholar 

  49. Krafczyk N, Heinrich T, Porzel A, Glomb MA (2009a) Oxidation of the dihydrochalcone aspalathin leads to dimerization. J Agric Food Chem 57:6838–6843. https://doi.org/10.1021/jf901614y

    CAS  Article  PubMed  Google Scholar 

  50. Krafczyk N, Woyand F, Glomb MA (2009b) Structure-antioxidant relationship of flavonoids from fermented rooibos. Mol Nutr Food Res 53:635–642. https://doi.org/10.1002/mnfr.200800117

    CAS  Article  PubMed  Google Scholar 

  51. Kreuz S, Joubert E, Waldmann KH, Ternes W (2008) Aspalathin, a flavonoid in Aspalathus linearis (rooibos), is absorbed by pig intestine as a C-glycoside. Nutr Res 28:690–701. https://doi.org/10.1016/j.nutres.2008.08.002

    CAS  Article  PubMed  Google Scholar 

  52. Ku SK, Lee W, Kang M, Bae JS (2015) Antithrombotic activities of aspalathin and nothofagin via inhibiting platelet aggregation and FIIa/FXa. Arch Pharm Res 38:1080–1089. https://doi.org/10.1007/s12272-014-0501-7

    CAS  Article  PubMed  Google Scholar 

  53. Kwak S, Han MS, Bae JS (2015) Aspalathin and nothofagin from rooibos (Aspalathus linearis) inhibit endothelial protein C receptor shedding in vitro and in vivo. Fitoterapia 100:179–186. https://doi.org/10.1016/j.fitote.2014.12.002

    CAS  Article  PubMed  Google Scholar 

  54. Layman JI, Pereira DL, Chellan N et al (2019) A histomorphometric study on the hepatoprotective effects of a green rooibos extract in a diet-induced obese rat model. Acta Histochem 121:646–656. https://doi.org/10.1016/j.acthis.2019.05.008

    CAS  Article  PubMed  Google Scholar 

  55. Lee W, Bae JS (2015) Anti-inflammatory effects of Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) In Vitro and In Vivo. Inflammation 38:1502–1516. https://doi.org/10.1007/s10753-015-0125-1

    CAS  Article  PubMed  Google Scholar 

  56. Lee W, Kim KM, Bae JS (2015) Ameliorative effect of aspalathin and nothofagin from rooibos (Aspalathus linearis) on HMGB1-induced septic responses In Vitro and In Vivo. Am J Chin Med 43:991–1012. https://doi.org/10.1142/S0192415X15500573

    CAS  Article  PubMed  Google Scholar 

  57. Lin K, Lin H, Chou P (2000) The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study. J Rheumatol 27:1501–1505

    CAS  PubMed  Google Scholar 

  58. Liu W, Wang H, Meng F (2015) In silico modeling of aspalathin and nothofagin against SGLT2. J Theor Comput Chem 14:1–14. https://doi.org/10.1142/S021963361550056X

    CAS  Article  Google Scholar 

  59. Magcwebeba TU, Riedel S, Swanevelder S et al (2016) The potential role of polyphenols in the modulation of skin cell viability by Aspalathus linearis and Cyclopia spp. herbal tea extracts in vitro. J Pharm Pharmacol 68:1440–1453. https://doi.org/10.1111/jphp.12629

    CAS  Article  PubMed  Google Scholar 

  60. Manley M, Joubert E, Botha M (2006) Quantification of the major phenolic compounds, soluble solid content and total antioxidant activity of green rooibos (Aspalathus linearis) by means of near infrared spectroscopy. J Near Infrared Spectrosc 14:213–222. https://doi.org/10.1255/jnirs.638

    CAS  Article  Google Scholar 

  61. Marnewick J, Joubert E, Joseph S et al (2005) Inhibition of tumour promotion in mouse skin by extracts of rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia), unique South African herbal teas. Cancer Lett 224:193–202. https://doi.org/10.1016/j.canlet.2004.11.014

    CAS  Article  PubMed  Google Scholar 

  62. Mazibuko-Mbeje SE, Dludla PV, Johnson R et al (2019) Aspalathin, a natural product with the potential to reverse hepatic insulin resistance by improving energy metabolism and mitochondrial respiration. PLoS ONE 14:1–16. https://doi.org/10.1371/journal.pone.0216172

    Article  Google Scholar 

  63. Mazibuko SE, Joubert E, Johnson R et al (2015) Aspalathin improves glucose and lipid metabolism in 3T3-L1 adipocytes exposed to palmitate. Mol Nutr Food Res 59:2199–2208. https://doi.org/10.1002/mnfr.201500258

    CAS  Article  PubMed  Google Scholar 

  64. Mazibuko SE, Muller CJF, Joubert E et al (2013) Amelioration of palmitate-induced insulin resistance in C2C12 muscle cells by rooibos (Aspalathus linearis). Phytomedicine 20:813–819. https://doi.org/10.1016/j.phymed.2013.03.018

    CAS  Article  PubMed  Google Scholar 

  65. Mertens N, Heymann T, Glomb MA (2020) Oxidative Fragmentation of Aspalathin Leads to the Formation of Dihydrocaffeic Acid and the Related Lysine Amide Adduct. J Agric Food Chem.https://doi.org/10.1021/acs.jafc.9b07689

  66. Mikami N, Tsujimura J, Sato A et al (2015) Green rooibos extract from Aspalathus linearis, and its component, aspalathin, suppress elevation of blood glucose levels in mice and inhibit α-amylase and α-glucosidase activities in vitro. Food Sci Technol Res 21:231–240

    CAS  Article  Google Scholar 

  67. Millar DA, Bowles S, Windvogel SL et al (2020) Effect of rooibos (Aspalathus linearis) extract on atorvastatin-induced toxicity in C3A liver cells. J Cell Physiol 235:9487–9496. https://doi.org/10.1002/jcp.29756

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. Moens C, Bensellam M, Himpe E et al (2020) Aspalathin protects insulin-producing β cells against glucotoxicity and oxidative stress-induced cell death. Mol Nutr Food Res 64:1–10. https://doi.org/10.1002/mnfr.201901009

    CAS  Article  Google Scholar 

  69. Morton J (1983) Rooibos tea, aspalathus linearis, a caffeineless, low-tannin beverage. Econ Bot 37:164–173. https://doi.org/10.1007/BF02858780

    Article  Google Scholar 

  70. Muller CJF, Joubert E, De Beer D et al (2012) Acute assessment of an aspalathin-enriched green rooibos (Aspalathus linearis) extract with hypoglycemic potential. Phytomedicine 20:32–39. https://doi.org/10.1016/j.phymed.2012.09.010

    CAS  Article  PubMed  Google Scholar 

  71. Muller M, De Beer D, Truzzi C et al (2020) Cold brewing of rooibos tea affects its sensory profile and physicochemical properties compared to regular hot, and boiled brewing. Lwt 132:109919. https://doi.org/10.1016/j.lwt.2020.109919

    CAS  Article  Google Scholar 

  72. Müller P, Downard KM (2015) Catechin inhibition of influenza neuraminidase and its molecular basis with mass spectrometry. J Pharm Biomed Anal 111:222–230. https://doi.org/10.1016/j.jpba.2015.03.014

    CAS  Article  PubMed  Google Scholar 

  73. Muller CJF, Malherbe CJ, Chellan N et al (2018) Potential of rooibos, its major C-glucosyl flavonoids, and Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid in prevention of metabolic syndrome. Crit Rev Food Sci Nutr 58:227–246. https://doi.org/10.1080/10408398.2016.1157568

    CAS  Article  PubMed  Google Scholar 

  74. Najafian M, Najafian B, Najafian Z (2016) The effect of aspalathin on levels of sugar and lipids in streptozotocin-induced diabetic and normal rats. Zahedan J Res Med Sci. (In Press)https://doi.org/10.17795/zjrms-4963

  75. OECD (2002) Glossary of statistical terms. OECD, Paris

    Google Scholar 

  76. Orlando P, Chellan N, Louw J, et al (2019) Aspalathin-rich green rooibos extract lowers LDL-cholesterol and oxidative status in high-fat diet-induced diabetic Vervet monkeys patrick. Molecules

  77. Pantsi WG, Marnewick JL, Esterhuyse AJ et al (2011) Rooibos (Aspalathus linearis) offers cardiac protection against ischaemia/reperfusion in the isolated perfused rat heart. Phytomedicine 18:1220–1228. https://doi.org/10.1016/j.phymed.2011.09.069

    CAS  Article  PubMed  Google Scholar 

  78. Patel O, Muller C, Joubert E et al (2016) Inhibitory interactions of Aspalathus linearis (rooibos) extracts and compounds, aspalathin and Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid, on cytochromes metabolizing hypoglycemic and hypolipidemic drugs. Molecules 21:1–13. https://doi.org/10.3390/molecules21111515

    CAS  Article  Google Scholar 

  79. Patel O, Muller CJF, Joubert E et al (2019) Pharmacokinetic interaction of green rooibos extract with atorvastatin and metformin in rats. Front Pharmacol 10:1–8. https://doi.org/10.3389/fphar.2019.01243

    CAS  Article  Google Scholar 

  80. Reichelt K V., Peter R, Roloff M, et al (2010) LC Taste® as a tool for the identification of taste modulsating compounds from traditional African teas. In: ACS Symposium Series. pp 61–74

  81. Riviere C (2016) Dihydrochalcones: Occurrence in the plant kingdom, chemistry, and biological activities. Stud Nat Prod Chem 51:253–381. https://doi.org/10.1016/B978-0-444-63932-5.00007-3

    CAS  Article  Google Scholar 

  82. Sagar T, Kasonga A, Baschant U et al (2020) Aspalathin from Aspalathus linearis (rooibos) reduces osteoclast activity and increases osteoblast activity in vitro. J Funct Foods 64:103616. https://doi.org/10.1016/j.jff.2019.103616

    CAS  Article  Google Scholar 

  83. Samodien S, Kock M de, Joubert E, et al (2020) Differential cytotoxicity of rooibos and green tea extracts against primary rat hepatocytes and human liver and colon cancer cells–causal role of major flavonoids. Nutr Cancer. pp 1–15https://doi.org/10.1080/01635581.2020.1820054

  84. SARC (2019) Rooibos industry fact sheet. https://sarooibos.co.za/faq/

  85. Schloms L, Storbeck KH, Swart P et al (2012) The influence of Aspalathus linearis (Rooibos) and dihydrochalcones on adrenal steroidogenesis: quantification of steroid intermediates and end products in H295R cells. J Steroid Biochem Mol Biol 128:128–138. https://doi.org/10.1016/j.jsbmb.2011.11.003

    CAS  Article  PubMed  Google Scholar 

  86. Schloms L, Swart AC (2014) Rooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes, modulating steroid hormone levels in H295R cells. Molecules 19:3681–3695. https://doi.org/10.3390/molecules19033681

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  87. Schulz H, Joubert E, Schütze W (2003) Quantification of quality parameters for reliable evaluation of green rooibos (Aspalathus linearis). Eur Food Res Technol 216:539–543. https://doi.org/10.1007/s00217-003-0696-1

    CAS  Article  Google Scholar 

  88. Shabalala SC, Dludla PV, Muller CJF et al (2019) Aspalathin ameliorates doxorubicin-induced oxidative stress in H9c2 cardiomyoblasts. Toxicol Vitr 55:134–139. https://doi.org/10.1016/j.tiv.2018.12.012

    CAS  Article  Google Scholar 

  89. Simpson MJ, Hjelmqvist D, López-Alarcón C et al (2013) Anti-peroxyl radical quality and antibacterial properties of rooibos infusions and their pure glycosylated polyphenolic constituents. Molecules 18:11264–11280. https://doi.org/10.3390/molecules180911264

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. Sissing L, Marnewick J, De Kock M et al (2011) Modulating effects of rooibos and honeybush herbal teas on the development of esophageal papillomas in rats. Nutr Cancer 63:600–610. https://doi.org/10.1080/01635581.2011.539313

    CAS  Article  PubMed  Google Scholar 

  91. Skibola CF, Smith MT (2000) Potential health impacts of excessive flavonoid intake. Free Radic Biol Med 29:375–383

    CAS  Article  Google Scholar 

  92. Smit SE, Johnson R, van Vuuren MA, Huisamen B (2018) Myocardial glucose clearance by aspalathin treatment in young, mature, and obese insulin-resistant rats. Planta Med 84:75–82. https://doi.org/10.1055/s-0043-117415

    CAS  Article  PubMed  Google Scholar 

  93. Snijman PW, Joubert E, Ferreira D et al (2009) Antioxidant activity of the dihydrochalcones aspalathin and nothofagin and their corresponding flavones in relation to other rooibos (Aspalathus linearis) flavonoids, epigallocatechin gallate, and trolox. Agric Food Chem 57:6678–6684. https://doi.org/10.1021/jf901417k

    CAS  Article  Google Scholar 

  94. Snijman PW, Swanevelder S, Joubert E et al (2007) The antimutagenic activity of the major flavonoids of rooibos (Aspalathus linearis): some dose- response effects on mutagen activation-flavonoid interactions. Mutat Res 631:111–123

    CAS  Article  Google Scholar 

  95. Son MJ, Minakawa M, Miura Y, Yagasaki K (2013) Aspalathin improves hyperglycemia and glucose intolerance in obese diabetic ob/ob mice. Eur J Nutr 52:1607–1619. https://doi.org/10.1007/s00394-012-0466-6

    CAS  Article  PubMed  Google Scholar 

  96. Stalmach A, Mullen W, Pecorari M et al (2009) Bioavailability of C-linked dihydrochalcone and flavanone glucosides in humans following ingestion of unfermented and fermented rooibos teas. J Agric Food Chem 57:7104–7111. https://doi.org/10.1021/jf9011642

    CAS  Article  PubMed  Google Scholar 

  97. Stander EA, Williams W, Rautenbach F et al (2019) Visualization of Aspalathin in Rooibos (Aspalathus linearis) Plant and Herbal Tea Extracts Using Thin-Layer Chromatography. Molecules 24:1–11. https://doi.org/10.3390/molecules24050938

    CAS  Article  Google Scholar 

  98. Stander MA, Van Wyk BE, Taylor MJC, Long HS (2017) Analysis of Phenolic Compounds in Rooibos Tea (Aspalathus linearis) with a Comparison of Flavonoid-Based Compounds in Natural Populations of Plants from Different Regions. J Agric Food Chem 65:10270–10281. https://doi.org/10.1021/acs.jafc.7b03942

    CAS  Article  PubMed  Google Scholar 

  99. Ulična´ O, Vančova´ O, Kucharska´ J, et al (2019) Rooibos tea (Aspalathus linearis) amelioratesthe CCl4-induced injury to mitochondrial respiratory function and energy production in rat liver. Gen Physiol Biophys 38:15–25

    Article  Google Scholar 

  100. van der Merwe JD, de Beer D, Joubert E, Gelderblom WCA (2015) Short-term and sub-chronic dietary exposure to aspalathin-enriched green rooibos (Aspalathus linearis) extract affects rat liver function and antioxidant status. Molecules 20:22674–22690. https://doi.org/10.3390/molecules201219868

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  101. van der Merwe JD, Joubert E, Manley M et al (2010) In vitro hepatic biotransformation of aspalathin and nothofagin, dihydrochalcones of rooibos (Aspalathus linearis), and assessment of metabolite antioxidant activity. J Agric Food Chem 58:2214–2220. https://doi.org/10.1021/jf903917a

    CAS  Article  PubMed  Google Scholar 

  102. van der Merwe JD, Joubert E, Richards ES et al (2006) A comparative study on the antimutagenic properties of aqueous extracts of Aspalathus linearis (rooibos), different Cyclopia spp. (honeybush) and Camellia sinensis teas. Mutat Res 611:42–53

    Article  Google Scholar 

  103. van Heerden FR, van Wyk BE, Viljoen AM, Steenkamp PA (2003) Phenolic variation in wild populations of Aspalathus linearis (rooibos tea). Biochem Syst Ecol 31:885–895. https://doi.org/10.1016/S0305-1978(03)00084-X

    CAS  Article  Google Scholar 

  104. Viraragavan A, Hlengwa N, De Beer D et al (2020) Model development for predicting: In vitro bio-capacity of green rooibos extract based on composition for application as screening tool in quality control. Food Funct 11:3084–3094. https://doi.org/10.1039/c9fo02480h

    CAS  Article  PubMed  Google Scholar 

  105. Walters NA, de Villiers A, Joubert E, de Beer D (2017) Improved HPLC method for rooibos phenolics targeting changes due to fermentation. J Food Compos Anal 55:20–29. https://doi.org/10.1016/j.jfca.2016.11.003

    CAS  Article  Google Scholar 

  106. Xue Y, Liu Y, Xie Y, et al (2020)Antioxidant activity and mechanism of dihydrochalcone C-glycosides: Effects of C-glycosylation and hydroxyl groups. Phytochemistry. 179https://doi.org/10.1016/j.phytochem.2020.112393

  107. Yadav NK, Shukla P, Omer A, Singh RK (2013) In silico approach to uncover the anti-cancerous activity of certain phyto-compounds. Gene Ther Mol Biol 15:147–158

    Google Scholar 

  108. Yang S, Lee C, Lee BS et al (2018) Renal protective effects of aspalathin and nothofagin from rooibos (Aspalathus linearis) in a mouse model of sepsis. Pharmacol Reports 70:1195–1201. https://doi.org/10.1016/j.pharep.2018.07.004

    CAS  Article  Google Scholar 

  109. Yepremyan A, Salehani B, Minehan TG (2010) Concise total syntheses of aspalathin and nothofagin. Org Lett 12:1580–1583. https://doi.org/10.1021/ol100315g

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  110. Zupic I, Cater T (2015) Bibliometric methods in management and organization. Organ. Res. Methods 18:429–472. https://doi.org/10.1177/1094428114562629

    Article  Google Scholar 

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Acknowledgements

The work was financially supported by the National Research Foundation of South Africa and the South African Medical Research Council.

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Chaudhary, S.K., Sandasi, M., Makolo, F. et al. Aspalathin: a rare dietary dihydrochalcone from Aspalathus linearis (rooibos tea). Phytochem Rev (2021). https://doi.org/10.1007/s11101-021-09741-9

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Keywords

  • Aspalathin
  • Aspalathus linearis
  • Dihydrochalcone
  • Rooibos
  • Bibliometrics
  • Anti-oxidant